4.6 Article

Cardiovascular risk prediction in the general population with use of suPAR, CRP, and Framingham Risk Score

Journal

INTERNATIONAL JOURNAL OF CARDIOLOGY
Volume 167, Issue 6, Pages 2904-2911

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.ijcard.2012.07.018

Keywords

Biomarkers; Cardiovascular risk; C-reactive protein; Framingham Risk Score; Soluble urokinase plasminogen activator receptor

Funding

  1. Danish Heart Foundation
  2. Danish Medical Association Research Fund/Volten
  3. Danish Pharmaceutical Association
  4. Lundbeck Foundation
  5. Novo Nordisk Foundation
  6. Novo Nordisk Fonden [NNF13OC0003736] Funding Source: researchfish

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Background: The inflammatory biomarkers soluble urokinase plasminogen activator receptor (suPAR) and C-reactive protein (CRP) independently predict cardiovascular disease (CVD). The prognostic implications of suPAR and CRP combined with Framingham Risk Score (FRS) have not been determined. Methods: From 1993 to 1994, baseline levels of suPAR and CRP were obtained from 2315 generally healthy Danish individuals (mean [SD] age: 53.9 [10.6] years) who were followed for the composite outcome of ischemic heart disease, stroke and CVD mortality. Results: During a median follow-up of 12.7 years, 302 events were recorded. After adjusting for FRS, women with suPAR levels in the highest tertile had a 1.74-fold (95% confidence interval [CI]: 1.08-2.81, p=0.027) and men a 2.09-fold (95% CI: 1.37-3.18, p<0.001) increase in risk compared to the lowest tertile. Including suPAR and CRP together resulted in stronger risk prediction with a 3.30-fold (95% CI: 1.36-7.99, p<0.01) increase for women and a 3.53-fold (1.78-7.02, p<0.001) increase for men when both biomarkers were in the highest compared to the lowest tertile. The combined extreme tertiles of suPAR and CRP reallocated individuals predicted to an intermediate 10-year risk of CVD of 10-20% based on FRS, to low (<10%) or high (>20%) risk categories, respectively. This was reflected in a significant improvement of C statistics for men (p=0.034) and borderline significant for women (p=0.054), while the integrated discrimination improvement was highly significant (P <= 0.001) for both genders. Conclusions: suPAR provides prognostic information of CVD risk beyond FRS and improves risk prediction substantially when combined with CRP in this setting. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

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